The current “gold standard” for skin replacement is the use of autologous skin grafts. However, due to donor-site tissue availability, complex maintenance and costs of such tissues, this treatment is often limited for patients. Also, most current engineered skins or skin substitutes do not fully recapitulate native skin as they are devoid of multiple skin cell types and structures like trilayers and dermal appendages. The current commercially available skin cellular models are also limited as they only use either immortalized cell lines derived from skin tumors or one or two primary cell types (e.g., keratinocytes and/or dermal fibroblasts) to be simple; thus they do not well represent and replicate the complexity of in vivo skin.
E. Bellas et al., In vitro 3D full thickness skin equivalent tissue model using silk and collagen biomaterials, Macromol. Biosci 12, 1627-1636 (2012), utilize adipose derived stem cells, keratinocytes, and fibroblasts to created a tri-layer skin-like product, but require the use of a silk scaffold onto which cells are seeded.
A. Skardal et al., Bioprinted Amniotic Fluid-Derived Stem Cells Accelerate Healing of Large Skin Wounds, Stem Cells Translational Medicine 1, 792-802 (2012), describes bioprinting of a skin-substitute directly onto a large wound, but use only amniotic fluid stem cells and bone-marrow-derived mesenchymal stem cells.
A. Monfort et al., Production of a human tissue-engineered skin trilayer on a plasma-based hypodermis, J Tissue Eng. Regen. Med. 7, 479-490 (2013), describes a skin-like trilayer product, but employed only adipogenic cells, fibroblasts, and keratinocytes, and used sequential culturing techniques that required 35 days to complete. Id. at 480-81.
V. Lee et al., Design and Fabrication of Human Skin by Three-Dimensional l3ioprinting, Tissue Engineering 20, 473-484 (2014), describe a skin-like product, created with 3D bioprinting, but utilize only keratinocytes and fibroblasts, printed between separate collagen layers. See, e.g., FIG. 2 therein.
Based on the foregoing, there remains a need for improved skin substitute products that can be used for therapeutic, and drug testing, purposes.